7-55191757-C-T

Position:

chr7-55191757-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_005228.5(EGFR):c.2508C>T(p.Arg836=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0213 in 1,613,938 control chromosomes in the GnomAD database, including 479 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 33 hom., cov: 32)

Exomes 𝑓: 0.022 ( 446 hom. )

Consequence

EGFR
NM_005228.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -3.31

Variant links:

Genes affected

EGFR (HGNC:3236): (epidermal growth factor receptor) The protein encoded by this gene is a transmembrane glycoprotein that is a member of the protein kinase superfamily. This protein is a receptor for members of the epidermal growth factor family. EGFR is a cell surface protein that binds to epidermal growth factor, thus inducing receptor dimerization and tyrosine autophosphorylation leading to cell proliferation. Mutations in this gene are associated with lung cancer. EGFR is a component of the cytokine storm which contributes to a severe form of Coronavirus Disease 2019 (COVID-19) resulting from infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). [provided by RefSeq, Jul 2020]

EGFR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 7-55191757-C-T is Benign according to our data. Variant chr7-55191757-C-T is described in ClinVar as [Benign]. Clinvar id is 45281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-55191757-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.31 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.016 (2440/152134) while in subpopulation NFE AF= 0.0241 (1641/67998). AF 95% confidence interval is 0.0232. There are 33 homozygotes in gnomad4. There are 1190 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFR	NM_005228.5 linkuse as main transcript	c.2508C>T	p.Arg836=	synonymous_variant	21/28	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7 linkuse as main transcript	c.2508C>T	p.Arg836=	synonymous_variant	21/28	1	NM_005228.5	ENSP00000275493	P1	P00533-1
EGFR	ENST00000455089.5 linkuse as main transcript	c.2373C>T	p.Arg791=	synonymous_variant	20/26	1		ENSP00000415559
EGFR	ENST00000450046.2 linkuse as main transcript	c.2349C>T	p.Arg783=	synonymous_variant	21/28	4		ENSP00000413354
EGFR	ENST00000700145.1 linkuse as main transcript	c.858C>T	p.Arg286=	synonymous_variant	8/9			ENSP00000514824

Frequencies

GnomAD3 genomes

AF:

0.0161

AC:

2441

AN:

152016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00464

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.00635

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00497

Gnomad FIN

AF:

0.0378

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0241

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.0165

AC:

4153

AN:

251218

Hom.:

AF XY:

0.0166

AC XY:

2255

AN XY:

135764

show subpopulations

Gnomad AFR exome

AF:

0.00283

Gnomad AMR exome

AF:

0.00416

Gnomad ASJ exome

AF:

0.0159

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00376

Gnomad FIN exome

AF:

0.0383

Gnomad NFE exome

AF:

0.0245

Gnomad OTH exome

AF:

0.0127

GnomAD4 exome

AF:

0.0219

AC:

31945

AN:

1461804

Hom.:

446

Cov.:

AF XY:

0.0212

AC XY:

15445

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00281

Gnomad4 AMR exome

AF:

0.00461

Gnomad4 ASJ exome

AF:

0.0145

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00348

Gnomad4 FIN exome

AF:

0.0356

Gnomad4 NFE exome

AF:

0.0251

Gnomad4 OTH exome

AF:

0.0186

GnomAD4 genome

AF:

0.0160

AC:

2440

AN:

152134

Hom.:

Cov.:

AF XY:

0.0160

AC XY:

1190

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00463

Gnomad4 AMR

AF:

0.00634

Gnomad4 ASJ

AF:

0.0138

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00477

Gnomad4 FIN

AF:

0.0378

Gnomad4 NFE

AF:

0.0241

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.0178

Hom.:

Bravo

AF:

0.0129

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0196

EpiControl

AF:

0.0186

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 19, 2021	This variant is associated with the following publications: (PMID: 24899223, 22192147) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 13, 2023	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Quest Diagnostics Nichols Institute San Juan Capistrano	May 28, 2021	- -
Benign, no assertion criteria provided	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Aug 24, 2007	- -

EGFR-related lung cancer

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Lung cancer

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.4

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over